| First Author | Sergeeva IA | Year | 2016 |
| Journal | Development | Volume | 143 |
| Issue | 12 | Pages | 2135-46 |
| PubMed ID | 27048739 | Mgi Jnum | J:235687 |
| Mgi Id | MGI:5800379 | Doi | 10.1242/dev.132019 |
| Citation | Sergeeva IA, et al. (2016) Identification of a regulatory domain controlling the Nppa-Nppb gene cluster during heart development and stress. Development 143(12):2135-46 |
| abstractText | The paralogous genes Nppa and Nppb are organized in an evolutionarily conserved cluster and provide a valuable model for studying co-regulation and regulatory landscape organization during heart development and disease. Here, we analyzed the chromatin conformation, epigenetic status and enhancer potential of sequences of the Nppa-Nppb cluster in vivo Our data indicate that the regulatory landscape of the cluster is present within a 60-kb domain centered around Nppb Both promoters and several potential regulatory elements interact with each other in a similar manner in different tissues and developmental stages. The distribution of H3K27ac and the association of Pol2 across the locus changed during cardiac hypertrophy, revealing their potential involvement in stress-mediated gene regulation. Functional analysis of double-reporter transgenic mice revealed that Nppa and Nppb share developmental, but not stress-response, enhancers, responsible for their co-regulation. Moreover, the Nppb promoter was required, but not sufficient, for hypertrophy-induced Nppa expression. In summary, the developmental regulation and stress response of the Nppa-Nppb cluster involve the concerted action of multiple enhancers and epigenetic changes distributed across a structurally rigid regulatory domain. |
